Tuberculosis is a leading cause of morbidity and mortality worldwide with more than 8 million new cases per year and approximately 2 million deaths (World Health Organization. Tuberculosis. Fact Sheet No 104, 2004). In addition, approximately 1.86 billion people, a third of the world's population, are infected (Dye et al. JAMA 1999; 282:677-86). Tuberculosis is also a major cause of morbidity and mortality among children with an estimated annual death of 400,000 children in the developing countries (Kochi A. Tubercle 1992; 72:1-6). Infection acquired during childhood can serve as a reservoir for future illness, resulting in active disease during adolescence and adulthood.
The treatment of tuberculosis is complex, requiring the use of multiple medications for prolonged periods of time, in order to avoid the development of resistance. However, the demands of such regimens often result in poor compliance, and this has led to the emergence of multiple drug resistant (MDR) strains.
The dissemination of MDR tuberculosis in the population has the potential for high morbidity and mortality. Furthermore, tuberculosis is one of the main causes of death in AIDS patients, and so the AIDS epidemic coupled with the advent of MDR tuberculosis, pose a formidable threat to overcrowded populations centered in prisons, homeless shelters and such at-risk communities. However, since tuberculosis is air-borne, no segment of the world's population can be thoroughly insulated from it.
Directly observed therapy programs, established to address many of the difficulties associated with the care of infection and disease caused by Mycobacterium tuberculosis, were shown to be effective in certain areas of the world (Zumla et al. Trans R Soc Trop Med Hyg 1999; 93:113-7). However, such programs are costly and logistically complex (Id.) and may not be feasible in many parts of the world, particularly for underserved populations. Bacille Camette-Guérin (BCG), the only available vaccine against tuberculosis (TB) (Guerin C. The history of BCG. In: Rosenthal SR ed. Boston: Little, Brown & Co., 1957:48-53), was shown to prevent disseminated disease in young children but has not been effective in preventing pulmonary TB (Colditz et al., JAMA 1994; 271:698-702), which is the main form of TB. Furthermore, BCG is losing its efficacy against MDR strains. Considering the overwhelming problem of TB, the difficulties associated with its treatment, and the new potentially harmful prospects, there is an urgent need to develop more effective strategies for the prevention of TB.